Cats

EFFICACY CONFIRMATION: In controlled, double blind, 1:1 randomized field studies conducted in the United States, the efficacy of cefovecin was compared to cefadroxil. In these studies, the efficacy of a single injection of cefovecin was demonstrated to be non-inferior to twice daily oral administration of cefadroxil. The following rates reflect the population of animals in which clinical signs had been reduced to mild or absent 28 days after the completion of therapy:

Type of Infection

Dogs

Cats

Cefovecin

Cefadroxil

Cefovecin

Cefadroxil

Skin

109/117 (93.2%)

107/113 (94.7%)

106/108 (98.1%)

99/106 (93.4%)

Urinary Tract (cystitis)

100/109 (91.7%)

64/98 (65.3%)

NA

NA

There were no serious adverse events reported during clinical field studies with either cefovecin or cefadroxil. Bacterial pathogens isolated in clinical field studies are provided in the MICROBIOLOGY section.

Dosage and Administration

To deliver the appropriate dose, reconstitute CONVENIA Injectable Lyophile with 10 mL Sterile Water for Injection, USP. Shake and/or allow vial to sit until all material is visually dissolved.

CONVENIA Injectable Lyophile is to be administered as a single subcutaneous injection at a dosage of 8 mg/kg or 0.1 mL/kg. A single injection provides a full 14 day course of therapy. When indicated, a second subcutaneous injection of 8 mg/kg can be administered 14 days after the first dose to provide therapeutic levels for a total of 28 days. Factors to be considered in the determination of an additional dose are the nature and severity of the infection, the susceptibility of the pathogen, and the immune status of the animal. Susceptibility of bacterial pathogens should be determined prior to treatment. Therapy with CONVENIA Injectable Lyophile may be initiated before the results of these tests are known. If acceptable response to treatment is not observed, then the diagnosis should be re-evaluated and appropriate alternative therapy considered.

Clinical Pharmacology

Cefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linear kinetics are exhibited (plasma concentrations do not increase proportionally with dose). Cefovecin does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the urine. Excretion of unchanged drug in the bile is a minor route of elimination. In vitro protein binding is greater than 98% in dog and cat plasma.

Pharmacokinetic parameters following subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Figures 2a, and 2b, and in Table 1.

Figure 2a: Mean Plasma and Urine Concentrations following a Single 8 mg/kg Subcutaneous Dosage of CONVENIA Injectable Lyophile in Dogs.

Figure 2b: Mean Plasma and Urine Concentrations following a Single 8 mg/kg Subcutaneous Dosage of CONVENIA Injectable Lyophile in Cats.

Table 1: Pharmacokinetic Parameters of a Single 8 mg/kg Subcutaneous Dosage of CONVENIA Injectable Lyophile in Dogs and Cats

Parameter

Estimate (± Standard Deviation)

Dogs

Cats

Terminal plasma elimination half-life, T1/2 (h)

133.1 (15.9)

170.7 (20.8)

AUC0-inf (µg•h/mL)

12130 (2492)

29023 (8267)

Time of maximum concentration, Tmax (h)

6.2 (3.0)

1.5 (1.5)

Maximum concentration, Cmax (µg/mL)

121.1 (50.75)

178.6 (42.7)

MICROBIOLOGY: CONVENIA Injectable Lyophile is a broad-spectrum cephalosporin with activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria including β-lactamase producing strains. Like other cephalosporins, cefovecin is bactericidal resulting from inhibition of cell wall synthesis. All MICs were determined in accordance with the National Committee for Clinical Laboratory Standards (NCCLS).

Table 2: MIC Values of CONVENIA Injectable Lyophile Against Bacterial Pathogens Isolated From Skin and Urinary Tract Infections in Dogs Enrolled in Clinical Studies Conducted in the U.S. From 2001 to 2003.

*Correlation between in vitro susceptibility data and clinical response has not been determined.

Susceptibility Testing

The interpretive criteria proposed in this section were determined in accordance with the National Committee for Clinical Laboratory Standards (NCCLS).

Dilution Techniques: Quantitative methods are used to determine

antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth or agar) with standardized inoculum concentrations and standardized concentrations of cefovecin powder.

Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. This procedure uses paper disks impregnated with 30 µg cefovecin to test the susceptibility of microorganisms.

Cefovecin MIC values and zone diameters should be interpreted according to the following proposed breakpoint criteria:

MIC (µg/mL)

Zone diameter (mm)

Interpretation

≤ 2

≥ 23

Susceptible (S)

4

20 to 22

Intermediate (I)

≥ 8

≤ 19

Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable drug concentrations. A report of “Intermediate” is a technical buffer and isolates falling into this category should be retested. Alternatively, the organism may be successfully treated if the infection is in a body site where the drug is physiologically concentrated. A report of “Resistant” indicates that achievable drug concentrations are unlikely to be inhibitory and other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control organisms to control the technical aspects of the laboratory procedures. Cefovecin powder should produce the following MIC values in these quality control strains:

Control Strain

MIC (µg/mL)

Aerobes

Broth Microdilution

Agar Dilution

Escherichia coli ATCC 25922

0.5 to 2

NA

Staphylococcus aureus ATCC 29213

0.5 to 2

NA

Streptococcus pneumoniae ATCC 49619

0.12 to 0.5

NA

Hemophilus somnus ATCC 700025

0.001 to 0.008

NA

Actinobacillus pleuropneumoniae ATCC 27090

0.008 to 0.03

NA

Anaerobes

Bacteroides fragilis ATCC 25285

8 to 32

8 to 32

Brucella thetaiotaomicron ATCC 29741

16 to 28

16 to 64

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 µg cefovecin disk should produce the following zone diameters in these quality control strains:

Control Strain

Zone diameter (mm)

Streptococcus pneumoniae ATCC 49619

25 to 31

Staphylococcus aureus ATCC 25923

26 to 35

Hemophilus somnus ATCC 700025

38 to 51

Actinobacillus pleuropneumoniae ATCC 27090

34 to 43

Escherichia coli ATCC 25922

25 to 30

CONTRAINDICATIONS: CONVENIA should not be administered to dogs or cats with a known allergy to cephalosporins. In penicillin-allergic animals, CONVENIA Injectable Lyophile should be used with caution.

CAUTIONS: The safe use of CONVENIA Injectable Lyophile in animals less than 4 months of age, pregnant dogs, dogs used for breeding purposes or in lactating dogs has not been established. Safety has not been established for IM or IV administration or long-term use. The safe use of this product administered concomitantly with other protein-bound drugs has not been studied. Such drugs commonly used include NSAIDs, cardiac, anticonvulsant, and behavioral medications. When tested in an in vitro equilibrium dialysis system using canine and feline plasma, cefovecin has been shown to result in an increase in the free concentration of carprofen, furosemide, doxycycline and ketoconazole in dog plasma, and in the free concentration of furosemide and ketoconazole in cat plasma. The clinical relevance of these observations is unknown.

Positive direct Coombs’ test results and false positive reactions for glucose in the urine have been reported during treatment with some cephalosporin antibacterials. Transient leukopenias have been reported in humans receiving cephalosporins. Some antibacterials, including cephalosporins, can cause lowered albumin values due to interference with certain testing methods.

Warnings

Keep out of reach of children. Not for use in humans. Consult a physician in case of accidental human exposure. For use in dogs and cats only. Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. To limit the development of antimicrobial resistance:

- cefovecin should not be used in food-producing animals.

- the extra-label drug use of cefovecin is not recommended.

SAFETY: Laboratory and clinical field studies have demonstrated that CONVENIA Injectable Lyophile is well tolerated in dogs and cats after subcutaneous administration.

DOGS:

Sixty-three different pure breeds and 25 different mixed breeds were represented in the 393 dogs enrolled in clinical field studies and receiving CONVENIA. Injectable Lyophile 226 dogs completed the studies and were included in the efficacy analysis with no serious adverse events reported. CONVENIA Injectable Lyophile was used in dogs receiving other commonly used veterinary products such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, non-steroidal anti-inflammatory agents, and vaccines with no serious adverse events reported.

In a margin of safety study, CONVENIA Injectable Lyophile was administered subcutaneously to healthy 4-month old beagle dogs at 1.5, 4.5, and 7.5 times the label dosage (12, 36, or 60 mg/kg) at one-half the recommended treatment interval (once weekly) for 4 consecutive weeks with no significant adverse reactions. Transient swelling was observed at the injection site. There were no clinically significant changes in clinical pathology variables and no treatment related gross or histopathological changes.

In a separate 30-day drug tolerance study, healthy 7-month old beagle dogs were administered a single subcutaneous dose at 22.5 times the label dosage (180 mg/kg) with no significant adverse reactions. Transient edema was observed near the injection site. There were no treatment-related changes in clinical pathology, feed consumption, body weights or physical examination findings.

CATS:

Four different pure breeds and five different mixed breeds were represented in the 147 cats enrolled in clinical field studies and receiving CONVENIA Injectable Lyophile. 108 cats completed the studies and were included in the efficacy analysis with no serious adverse events reported. CONVENIA Injectable Lyophile was used in cats receiving other commonly used veterinary products such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, and vaccines with no serious adverse events reported.

In a margin of safety study, CONVENIA Injectable Lyophile was administered subcutaneously to healthy 4-month old domestic shorthair cats at 1.5, 4.5, and 7.5 times the label dosage (12, 36, or 60 mg/kg) at one-half the recommended treatment interval (once weekly) for 4 consecutive weeks with no significant adverse reactions. Over the 4-week treatment period, single incidents of soft stools were observed in 1 of 8 cats treated with 1.5 times the label dosage (12 mg/kg), 2 of 8 cats treated with 4.5 times the label dosage (36 mg/kg), and 1 of 8 cats treated with 7.5 times the label dosage (60 mg/kg). Two incidents each of soft or runny stools were observed in 2 of 8 cats treated with 7.5 times the label dosage (60 mg/kg). Transient swelling was observed at the injection site. There were no clinically significant changes in clinical pathology variables and no treatment related gross or histopathological changes.

In a separate 30-day drug tolerance study, healthy 7-month old domestic shorthair cats were administered a single subcutaneous dose at 22.5 times the label dosage (180 mg/kg) with no significant adverse reactions. Transient edema was observed at or near the injection site. There were no treatment-related changes in clinical pathology, feed consumption, body weights or physical examination findings.

Adverse Reactions

There were no serious adverse events reported during clinical field studies with CONVENIA Injectable Lyophile. Abnormal health observations reported in cefovecin and cefadroxil-treated animals are summarized in Table 6.

Table 6: Number (Percentage) of Animals with Abnormal Health Observations Reported During Clinical Field Studies with CONVENIA Injectable Lyophile.

Abnormal Observation

Dogs

Cats

Cefovectin (N=226)

Cefadroxil (N=228)

Cefovectin (N=108)

Cefadroxil (N=106)

Lethargy

10 (4.4%)

22 (9.6%)

4 (3.7%)

7 (6.6%)

Inappetence / Decreased Appetite

13 (5.8%)

21 (9.2%)

6 (5.6%)

5 (4.7%)

Vomiting

11 (4.9%)

36 (15.8%)

9 (8.3%)

13 (12.3%)

Diarrhea / Soft Feces

13 (5.8%)

23 (10.1%)

7 (6.5%)

29 (27.4%)

Storage

Store un-reconstituted product in the original carton refrigerated at 2° to 8°C.

Store reconstituted product in the original carton refrigerated for up to 56 days. CONVENIA Injectable Lyophile should be protected from light. After each use it is important to return the unused portion back to the refrigerator in the original carton. As with other cephalosporins, the color of the solution may vary from clear to amber at reconstitution and may darken over time. Solution color does not adversely affect potency.

PRESENTATION:CONVENIA Injectable Lyophile is available as a single 80 mg/mL multi-use vial containing cefovecin sodium as a lyophilized cake.

Zoetis is a trademark and Convenia is a registered trademark of Zoetis or its licensors, used under license by Zoetis Canada Inc.

Zoetis Canada Inc., Kirkland QC H9H 4M7

30224000

1520-11-0

NAC No.: 1198341.4

ZOETIS CANADA INC.16,740 TRANS-CANADA HIGHWAY, KIRKLAND, QC, H9H 4M7

Order Desk:

800-663-8888

Technical Services Canada:

800-461-0917

Technical Services USA:

800-366-5288

Website:

www.zoetis.ca

Every effort has been made to ensure the accuracy of the Convenia Injectable Lyophile information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.